Pemetrexed disodium heptahydrate has the chemical name L-Glutamic acid, N-[4-[2-(2-amino-4,7-dihydro-4-oxo-1H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-, disodium salt, heptahydrate. The structural formula is as follows:

Pemetrexed is used in the treatment of malignant pleural mesothelioma and non-small cell lung cancer. The commercially-available product, ALIMTA, is supplied as a sterile lyophilized powder for intravenous infusion available in single-dose vials.
The relatively rapid formation of degradants is generally accepted as one of the factors which has prevented aqueous pemetrexed formulations having long-term stability from being commercially available. Five 5 major degradants of pemetrexed have been observed. Under acidic conditions, decarboxylation of glutamic acid is observed. Under alkaline conditions, degradation proceeds by side chain amide hydrolysis followed by deamination. In the presence of oxygen, two oxidative degradants result.
U.S. Pat. No. 6,686,365 discloses that ready to use (RTU) formulations of pemetrexed, which contain monothioglycerol, L-cysteine or thioglycolic acid. The '365 patent also disclosed that formulations which can be stored at room temperature are desirable. However, pemetrexed-containing formulations containing one of monothioglycerol, L-cysteine or thioglycolic acid referred to in the '365 patent when included at their recommended concentrations of 2.4 mg/ml, together with pemetrexed at a concentration of 25 mg/ml failed to demonstrate sufficient long term stability. The drug content fell well below acceptable levels.
There is a need to provide RTU liquid formulations of pemetrexed that have long term storage stability.